Ethnic, racial and migrant inequalities in respiratory health

Disparities in the incidence, prevalence, and morbidity and mortality rates of many respiratory diseases are evident among ethnic groups. Biological, cultural and environmental factors related to ethnicity can all contribute to the differences in respiratory health observed among ethnic minority groups, but the inequalities observed are most commonly due to lower socioeconomic position. People who migrate within a country or across an international border may experience an improvement in respiratory health associated with improvements in socioeconomic position. However, migrants may also experience worse health outcomes in destination countries, as they are faced by barriers in language and culture, discrimination, exclusion and limited access to health services. While some high-quality studies investigating ethnicity and respiratory health are available, further research into ethnic differences is needed. Improving the recording of ethnicity in health records, addressing barriers to accessing respiratory healthcare and improving cultural literacy more generally are some of the ways that inequalities can be tackled.Copyright © ERS 2023.

Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

Characterization of Patients with Type 2 Diabetes Mellitus and covid-19 in Primary Care

Summary Objectives: To describe the characteristics of the population diagnosed with type 2 Diabetes Mellitus (dm2) infected by sars-CoV-2, and to evaluate whether there is an association between dm2 history and covid-19 severity. Method(s): non-probabilistic by convenience sampling, information was obtained from the Online Notification System for Epidemiological Surveillance (sinolave) of the Family Medicine Unit No. 28 of the Mexican Institute of Social Security. A total of 1688 confirmed cases of covid-19 were identified and grouped into patients with and without dm2. Bivariate statistical analysis was performed with Excel 2019 and Stata v. 15.1 programs;measures of association were used using Poisson logistic regression and chi2 test with statistical significance <0.05. Result(s): it was observed that, in patients with covid-19 and dm2, the prevalence ratio of severe acute respiratory infection, diagnosis of pneumonia, hospitalization, and death were higher compared to the group without dm2. Conclusion(s): the frequency, of unfavorable characteristics, was higher in the group of patients with dm2. Health conditions caused by covid-19 reinforce the relevance of an intentional search for undiagnosed diabetic patients, untreated or under treatment with poor glycemic control, in order to avoid major health complications.Copyright © 2023, Universidad Nacional Autonoma de Mexico. All rights reserved.

Frequency of antibiotic prescribing in adults hospitalized for SARS-CoV-2 in a high complexity institution in Santiago de Cali, Colombia.

Objective: To determine the frequency of antibiotic use and to know which clinical and socio-demographic variables were related to the probability of suffering infections associated with COVID-19. Method(s): Adults hospitalized for COVID-19 who received one or more antibiotics during hospitalization were evaluated. We performed a descriptive analysis of variables in the general population' bivariate analysis in two groups (documented vs. suspected infection) and multivariate logistic regression of factors associated with mortality. Result(s): It was determined that 60.4% of adults hospitalized for COVID-19 received antibiotics. Coinfection was documented in 6.2% and superinfection in 23.3%. Gram-negative germs were reported in 75.8% of cultures, fungi in 17.8% and gram-positive in 14.2%. Variables such as age, comorbidities, ICU, anemia, steroids, mechanical ventilation, hemofiltration were statistically significantly related to documented infection. High-flow cannula was associated as a protective factor. Overall mortality was 43.9%, 57.8% in the first group and 38.1% in the second (p=0.002). Conclusion(s): There is a considerable frequency of antibiotic use in subjects hospitalized for COVID-19, particularly related to relevant findings of bacterial superinfection, in those with comorbidities, such as diabetes mellitus, immunosuppression, anemia and fragility, in whom the behavior of the disease is more severe and lethal.Copyright © 2023 Asociacion Colombiana de Infectologia. All rights reserved.

Screening and monitoring patients with COVID-19 pneumonia treated with immunosuppressive agents for hepatitis B reactivation.

Immunosuppressive drugs are used for treating coronavirus disease 2019COVID-19pneumonia. This study examined the current status of screening and monitoring patients with COVID-19 pneumonia treated with immunosuppressive agents for hepatitis B virusHBVreactivation. Of 123 patients whose hepatitis B surface antigen level was measured, 2 were HBsAg-positive. Antihepatitis B core/surface antibodies were measured in all 121 HBsAg-negative patients. HBV DNA was measured in 31 of 32 patients who were positive for either or both antihepatitis B core/surface antibodies. Of 34 patients requiring regular monitoring, only 4 were monitored. The HBV monitoring rate at the initiation of COVID-19 treatment was high. How-ever, HBV monitoring after COVID-19 treatment was difficult because most patients were transferred to other hospitals or had their treatment terminated.Copyright © 2022 Takeshi Matsui et al.

A pre-existing case of HBV infection with elevated HBV DNA after COVID-19 pneumonia treatment.

The patient presented with fever and appetite loss. Computed tomography (CT) revealed a moderate grade 2 pneumonia. Besides, further blood examination showed his HB antigen as negative, anti-HBs/c anti-body as positive, and HBV DNA level as 1.0 LIU/mL. Therefore, he was diagnosed with COVID-19. Administered treatments comprised oxygen inhalation and steroid therapy, including pulses, remdesivir, and baricitinib, which improved pneumonia. Interestingly, one month posttreatment, his HBV DNA level in-creased to 1.4 LIU/mL, followed by a further increase to 1.7 LIU/Ml, showing an improvement. Tenofovir alafenamide fumarate was thus administered. In clinical practice, immunosuppressive therapy is used for patients with moderate-to-severe COVID-19 pneumo-nia. However, close attention should also be paid to the elevation of blood HBV DNA levels during and after treatment.Copyright © 2022 The Japan Society of Hepatology.

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

New definition of RIME: Mucocutaneous eruptions, bullous lesions and multi-mucosal involvement

Objectives: A 14-year-old female patient presents with marked haemorrhagic, adherent crusting of the upper and lower lip and enoral vesicles and erosions. Two weeks before, she had suffered from a respiratory tract infection. She did not take antibiotics but ibuprofen. One week later, she described a swelling and crusting of the upper and lower lips. Urogenital mucosa was also erosive. There was no ocular involvement. Another week later, cocard-like single lesions with partly central blister formation developed. A flaccid blister of 15 mm in diameter was detected in the left ear helix. In total, there was a limited cutaneous involvement of <10% BSA. The girl was admitted to the paediatric clinic. Method(s): Due to mucocutaneous eruptions, bullous lesions and multimucosal involvement, we assumed a Steven-Johnson syndrome or reactive infectious mucocutaneous eruption (RIME). Intravenous rehydration and prophylactic administration of cefotaxime and aciclovir were given. She was balanced and given analgesia with novalgin. The recent increased intake of ibuprofen was discontinued. Local therapy included mometasone cream and serasept dressings. During the inpatient stay, the general condition stabilised and the skin efflorescence's showed a clear regression. Result(s): The microbiological smears for COVID-19, HSV, VZV, mycoplasma, and chlamydia were negative. Discussion(s): As adult classifications for blistering severe cutaneous adverse reactions are limited applicable in children, Ramien et al. proposed revised paediatric-focused clinical criteria 2021. They leave traditional definitions of EEM, SJS and TEN. But they distinguish erythema multiforme (EM) for classic targets with/without mucosal involvement, RIME for cases with mucosal predominance and a respiratory infection trigger, and drug-induced epidermal necrolysis (DEN) for cases caused by medications. (Ramien BJD 2021) There are no current guidelines for RIME therapy. A reasonable management approach includes symptomatic therapy, treatment of identifiable infectious triggers (if possible), consulting urologists, ophthalmologists and gynaecologists (if necessary), immunosuppression, and psychological support. (Ramien ClinExpDermatol 2021).

Immunosuppression and Covid-19: Risk factor or treatment?

Introduction: During the Covid-19 pandemic, 540,895 people were identified as immunosuppressed and believed to be at increased risk of severe disease.1 As the pandemic evolved, biologic immunosuppression became a treatment of severe Covid-19.2 The true impact of immunosuppression on disease severity remains unclear. Objective(s): 1. Identify the incidence of immunosuppressed patients admitted to the ICU. 2. Analyse the mortality of those who are immunocompetent and immunosuppressed. 3. Examine the differences in mortality and level of care required between sub groups of patients on immunosuppression;those on biologics, non-biologics, and a combination of both. Method(s): A retrospective search of all Covid-19 positive admissions from March 2020 to November 2021 across two adult ICUs at Chelsea & Westminster NHS Trust was performed, using the EPR system. We identified those on immunosuppressive drugs, the level of care they required, and 28 day mortality. We categorised different types of immunosuppression, vaccination status, if applicable and co-morbidities. The exclusion criteria were primarily those with false positive swabs or incomplete data. Result(s): Baseline characteristics were median age (56 vs 56), and APCHE II score (20.08 in the immunosuppressed group vs 14.0 in immunocompetent). Thirteen immunosuppressed patients were identified. Reasons for drug immunosuppression in this group included solid organ transplant (6/13), and autoimmune conditions (7/13). Two patients were on biologic drugs alone, 8 were on non-biologics, and 3 were on a combination. Four of this group had received at least 2 doses of a Covid-19 vaccine. Mortality was 61.54% (8/13) in the immunosuppressed group vs 36.65% (199/543) in the immunocompetent group. Conclusion(s): Despite similar demographics, patients on immunosuppression had a significantly higher mortality than the immunocompetent group. Interestingly, those on targeted biological immunosuppression had the lowest incidence of requiring level 3 care, and no deaths. It is a possibility that biologics dampen the hyper-inflammation seen in severe Covid-19 pneumonitis, raising the question of a possible protective benefit from severe disease. This reflects the findings of the REMAP-CAP investigators,3 who showed that the IL-6 inhibiting biologics Tocilizumab and Sarilumab are efficacious against the most severe disease following admission to ICU with Covid-19 pneumonitis. The single centre and retrospective observational design, combined with small numbers on immunosuppression, despite a large inclusion criterion, mean it is not possible to make statistical conclusions. Confounding factors include the effects of vaccination, shielding and the change in SARS-CoV-2 variant prevalent during different times during the pandemic.

SARS-CoV-2 infection and solid organ transplantation.

Transplantation has become a valid therapeutic option for an increasing number of patients with end-stage organ disease. The emergence of SARS-CoV-2 coronavirus infection and associated disease (COVID-19) has alarmed the transplant community, since recommendations for adequate follow-up of organ transplant recipients during the acute phase of a pandemic are limited. Furthermore, treatment options against COVID-19 disease and adequate adjustment of immunosuppression in at risk patients remain a concern. This review summarizes current knowledge on the incidence and clinical course of SARS-CoV-2 infection in patients with solid organ transplantation. It also discusses therapeutic strategies and provides general recommendations on how to proceed with transplantation programs in a time when health care resources may become scarce.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

COVID-19 vaccines in patients with solid tumor cancers receiving immune checkpoint inhibitors

Background: The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. It is unknown whether concurrent CPI and Sars-COV-2 vaccine administration increases the risk of irAEs. This retrospective study examined the incidence of severe irAEs in cancer patients receiving CPI therapy at the time of vaccination against Sars CoV-2. Method(s): Following IRB approval, pts with solid tumors who received any approved CPI since FDA authorization of the COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received one or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation of CPI due to irAE. Data was analyzed using descriptive statistics. Result(s): 290 pts with bladder, head/neck, liver, skin (melanoma, SCC), renal, and gynecologic cancer were included in analysis. The median age was 67 years (IQR: 59.0-74.0) and 66% pts were male. At the time of vaccination, 201 pts (69.3%) received CPI monotherapy, 53 pts (18.3%) received combination (combo) CPI therapy, and 36 pts (12.4%) received other therapies (chemo, TKIs, etc.) with CPI. The vaccine manufacturer was Pfizer Bio-N-Tech in 162 pts (55.9%), Moderna in 122 pts (42.1%), and Johnson and Johnson in 6 pts (2.1%). The number of vaccinations received was >/= 3 in 214 pts, 2 in 64 pts, and 1 in 11 pts. 30 pts (11.5%) experienced severe irAEs following vaccination. The rate of severe irAEs was 10.3% (30/290) in the total population [6% (12/201) with CPI monotherapy, 19% (10/53) with combo CPI, and 22% (8/36) in the combo CPI-other group]. Severe irAEs occurred after the first vaccine dose in 5 pts (16.7%), second dose in 16 pts (53.3%), and third dose in 9 pts (30%) pts. The median time between CPI treatment and vaccination in pts who experienced irAE was15.5 days (IQR: 10.2-23.0). Hospitalization was required for 19 patients (63.3%). 24 pts (80.0%) required immunosuppressive therapy with a median therapy duration of 98.5 days (IQR 40.2-173.0). 16 pts (53.5%) discontinued CPI therapy following severe irAEs Conclusion(s): In this retrospective study, we observed a 10.3% rate of severe irAE in cancer pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI.

A cross-sectional study on the seroprevalence of the SARS-CoV-2 IgG antibody in patients with cancer from central Kerala

Background: Patients with cancer are vulnerable to coronavirus disease 2019 (COVID-19). Given the rising number of COVID-19 cases and relaxation of stringent COVID-19 protocols, assessment of the level of protective immunity to COVID-19 in patients with cancer has assumed importance. Objective(s): Our primary objective was to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in patients with cancer. Material(s) and Method(s): We conducted a cross-sectional study on 100 patients with solid tumors attending our Oncology Department at the Believers Church Medical College, Kerala, India, between December 2020 and June 2021. Seroprevalence was assessed using the VITROS Anti-SARS-CoV-2 IgG test (Ortho-Clinical Diagnostics, Rochester, NY, USA). Additionally, we assessed the factors associated with seropositivity and collected data regarding the general experience of patients with cancer during the pandemic. Result(s): The median age of the participants was 62 years (IQR, 53-69.8);52 (52%) were males. The seroprevalence of the SARS-CoV-2 IgG antibodies was 11% (95% CI, 4.8-17.1). Age < 50 years was the only factor that was significantly associated with a higher rate of COVID-19 antibodies (77% vs 8.9% in patients >= 50 years;P = 0.007), and sex, smoking, and the use of alcohol did not show any association. The majority (77/100, 77%) of the patients were worried about contracting COVID-19 infection;some even deferred cancer-directed treatment because of the fear of visiting health care settings. Conclusion(s): Low seroprevalence of SARS-CoV-2 IgG antibodies in unvaccinated patients with cancer is a matter of concern as it indicates that many of these patients are still vulnerable to infection. There is an urgent need to continue implementing strict safety measures in oncology centers and to encourage widespread COVID-19 vaccination to prevent the uncontrolled spread of COVID-19 among patients with cancer. (Funded by the institution, Believers Church Medical College, Kerala).Copyright © 2023 Neurology India, Neurological Society of India Published by Wolters Kluwer - Medknow.

Outcomes of cancer patients with Covid-19 admitted to the Intensive Care Unit: A retrospective study

Introduction: Active cancer increases the odds of death among patients with COVID-19.1 Cancer patients may be at increased risk of complications and mortality from COVID-19 owing to the systemic effects of malignancy, immune suppression after chemotherapy, treatment-related complications and presence of co-morbidities.2 They may develop serious complications necessitating ICU admission. In a meta-analysis, the pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2%.3 Our hospital is a tertiary referral cancer centre, and the ICU admitted cancer patients with Covid-19 throughout the pandemic. Objective(s): To determine the 30-day in-hospital mortality of adult cancer patients with Covid-19 admitted to the ICU. We also aimed to determine the factors associated with mortality in cancer patients with Covid-19. Method(s): After approval from the Institutional Ethics Committee, data of all cancer patients (age = 16 years) with Covid-19 admitted to the ICU between March 2020 and March 2021 were retrieved from the hospital records. In case of multiple ICU admissions, data from the first admission was recorded. Data recorded included demographic details, type of cancer (solid, haematological), surgical status, APACHE-II and SOFA scores, C-reactive protein, and interventions in ICU. The primary outcome was 30-day in-hospital mortality. Data were analysed using Man-Whitney test and chi-square test. A multivariable regression analysis was carried out to determine factors associated with mortality. Result(s): Data of 127 cancer patients with Covid-19 was analysed. The median [interquartile range, IQR] age was 55 (43-62) years, and there were 50 females (39.3%). Comorbidities were present in 46 (36%) patients, the commonest being diabetes (29 patients) and hypertension (31 patients). The median [IQR] APACHE-II and SOFA scores were 15[8-20] and 4[2-7], respectively. Overall, 62/127 patients died, and 30-day hospital mortality was 49%. There were 30 patients with haematological malignancy and 97 with solid tumours with 30-day in-hospital mortality rates of 46.7% and 49.5%, respectively;p = 0.84). Amongst patients with solid tumours, there was no difference in mortality in surgical patients compared to non-surgical patients (43.3% vs. 52.2%;p = 0.42). Table 1 summarises the parameters and interventions in survivors and non-survivors. On multivariable analysis, only the change in SOFA score from Day 1 to Day 3 was independently associated with outcome (Odds ratio 1.36 (95% confidence interval 1.01-1.84, p-0.04). Conclusion(s): In patients with cancer and Covid-19 and age =16 years admitted to our ICU, the crude 30-day hospital mortality was 47%. There was no association of mortality with cancer type or surgical status. The only independent predictor of mortality was progression of organ failure. Cancer patients with Covid-19 have a reasonable outcome and should be given a trial of intensive care.

Exosomes/EVs: IMMUNOMODULATORY EFFECTS OF AMNITOIC FLUID EXTRACELLULAR VESICLES IN AN IN-VITRO MODEL OF IMMUNE ACTIVATION

Background & Aim: Amniotic fluid (AF)-derived EVs are currently under investigation for use as anti-inflammatory therapeutics in COVID-19 and COVID-19 long haulers. The dysregulation of the immune response induced by SARS-COV-2 is a key driver of both acute COVID-19 induced lung injury and long term COVID-19 sequela. There is a clear need to identify therapeutics that suppress excessive inflammation and reduce immune cell exhaustion to improve patient short term and long-term outcomes. Amniotic fluid (AF)- derived extracellular vesicles (EVs) have previously been shown to deliver anti-inflammatory and immune-modulatory signals to diverse cellular targets. We aimed to test if AF-EVs carry immune-suppressive molecules and can suppress T-cell immune activation and exhaustion in vitro. Methods, Results & Conclusion(s): The AF-EV biologic tested was derived from AF collected from consenting donors during planned, fullterm cesarean sections. AF was centrifuged and filtered to remove cellular debris and create a product containing AF-EVs and soluble extracellular components. Fluorescent EXODOT analysis was performed to demonstrate the presence of EV markers CD9, CD81, ALIX, and immune suppressive molecule PD-L1. T-cell activation/exhaustion was induced in vitro by treating human peripheral blood mononuclear cells with activation agent PHA for 3 days with the addition of AF-EVs or saline control. Immune activation/exhaustion was measured by flow cytometry to determine the expression of PD-1 on CD3+ T-cells. The AF-EV biologic was characterized to contain EVs with positive expression of CD9, CD81, ALIX, and PL-L1. T-cell activation/exhaustion was upregulated in response to PHA and was significantly reduced by 8% in AF-EV treated T-cells compared to saline control (77.7% vs 85.7%, respectively P<0.05). These findings demonstrate that AF-EVs do express PD-L1, a surface marker that has previously been demonstrated to contribute to exosome-mediated immunosuppression. Furthermore, we confirmed in vitro that AF-EVs suppress T-cell activation/ exhaustion in the presence of a T-cell activation agent. COVID-19 long haulers have been described to have upregulated and pro-longed immune activation and T-cell exhaustion, marked by an increase in PD1+ T-cells. Therefore, this finding serves as a starting point for the development of a potential mechanism of action that may describe AF-EV's therapeutic effect in COVID-19 long hauler patients.Copyright © 2023 International Society for Cell & Gene Therapy

Maxillary osteomyelitis secondary to mucormycosis, a sequel of COVID-19: a clinical case report

Introduction: One of the consequences of COVID-19 is the incidence of mucormycosis in the jaws and subsequent osteomyelitis in patients with undiagnosed or uncontrolled comorbidities, such as diabetes mellitus and associated immunosuppression. Case Report: A 52-year-old male patient with a history of COVID-19 two months ago presented a painful ulcerative lesion of insidious onset in the palatal raphe measuring approximately 2 mm. He referred to numbness of the palatal region of one month of evolution. During the physical examination, purulent content, multiple pustules in the anterior maxillary buccal mucosa, and mobility of upper anterior teeth were observed. The CT revealed isodense bilateral images in maxillary and ethmoidal sinuses, bone sequestrations, and partial loss of anterior vestibular cortical bone. Laboratory tests revealed no abnormality, except for HbH1c: 10.2gr/dl. The patient was hospitalized for control of newly diagnosed diabetes mellitus. Maxillary incisional biopsy was performed, and microscopic analysis showed a mixed inflammatory infiltrate, fibrin deposits with eosinophilic and birefringent ribbon-like hyphae, branched at right angles, compatible with maxillary osteomyelitis secondary to mucormycosis. The treatment started with antifungal and intravenous antibiotics, followed by surgical cleaning under general anesthesia. The patient progressed favorably. Conclusion(s): Immunosuppression resulting from COVID-19 and/or uncontrolled systemic diseases can condition the appearance of rare opportunistic microorganisms causing infections such as mucormycosis. Early diagnosis and treatment make a difference in the morbidity and mortality of patients.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

The Effect of FOXP3+Regulatory T Cells on Infectious and Inflammatory Diseases

CD4+CD25+FOXP3+regulatory T cells (Tregs) contribute to the maintenance of immune homeostasis and tolerance in the body. The expression levels and functional stability of FOXP3 control the function and plasticity of Tregs. Tregs critically impact infectious diseases, especially by regulating the threshold of immune responses to pathogenic microorganisms. The functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth, which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.Copyright © 2021. All rights reserved.

Cellular and humoral immune responses after SARS-CoV-2 vaccination in pediatric kidney recipients

Objective: Humoral and cellular immune responses to SARS-CoV-2 vaccination are reduced in adult kidney recipients. After pediatric kidney transplantation there are only few data available - mostly limited to monitoring of SARS-CoV-2 antibodies. Method(s): Cellular and humoral immune responses have been monitored before and after SARS-CoV-2 vaccination in pediatric kidney recipients. After in vitro stimulation with SARS-CoV-2 antigen (spike glycoprotein) virus-specific CD4 and CD8 T cells (SARS-CoV-2-Tvis) have been identified by cytokine flow cytometry. SARS-CoV-2 IgG was measured by CMIA. Result(s): Immune response after SARS-CoV-2 vaccination was analyzed in a total of 30 pediatric kidney recipients (age at 1st vaccine dose 5.2 - 17.8 years, median 14.8 years;43% male;30/30 2 vaccine doses;23/30 3 vaccine doses). At time of vaccination 22 patients (73%) received a tacrolimus (Tac)-based immunosuppression combined with mycophenolate mofetil (MMF;n = 15) or everolimus (n = 6) or neither of them (n = 1);3 patients were exposed to cyclosporine A and 5 patients to a calcineurin inhibitor (CNI)- free immunosuppression. MMF was used in 18/30 patients. After 1st dose of mRNA vaccine SARS-CoV-2 antibodies were detectable in 50% of pediatric kidney recipients, after 2nd dose in 78% and after 3rd dose in 88%. After the 2nd vaccine dose absence of humoral immune response (< 33.8 BAU/ml) was only found in case of MMF use (predominately combined with Tac). Peak IgG values (> 2,080 BAU/ml) were only detected in MMF-free regimens (6/7). Cellmediated response partially differed from humoral response, e. g., in some patients SARS-CoV2-Tvis were found despite lack of virus-specific antibodies. After 1st vaccine dose SARS-CoV-2-Tvis were detectable in 50% of pediatric kidney recipients, after 2nd dose in 92%. After 2nd vaccine dose absence or very low levels of SARS-CoV-2-Tvis (< 0.3 cells/mul) were only found in Tac-based immunosuppressive regimens, whereas higher levels (> 1.3 cells/mul) were exclusively detected in patients with MMFfree medication. Conclusion(s): After pediatric kidney transplantation humoral and cellular immune responses to SARS-CoV-2 vaccination were suboptimal, but more pronounced than in adult kidney recipients. Use of Tac and MMF was associated with impaired immune response to vaccination. SARS-CoV-2-specific humoral response corresponded only partially to cell-mediated response. Additional monitoring of SARS-CoV- 2-Tvis might be recommendable to improve assessment of the individual vaccine response and thereby to personalize the decision on the necessity of further vaccine doses.